- Email: [email protected]
EVALUATION OF KIDNEY-PRESERVATION METHODS
880 withdrawn from further issue by the C.S.L. in December, 1971,3 because of widespread reports of its lack of specificity, making it almost useless in the diagnosis of sarcoidosis. Cross-reactivitv with C.S.L. batch 004 material was noted in healthy volunteers, in patients with pulmonary tuberculosis, lung abscess, silicosis, chronic bronchitis, emphy-
idiopathic pulmonary fibrosis, lung carcinoma, and collagen disorders.4-6 There is a strong likelihood, then, that Israel and Goldstein’s findings were equally nonspecific and had resulted from the use of an unsatisfactory sema,
bulk batch of Kveim material. In sum, I think that we have not yet arrived at a position where we can safely make a-priori diagnoses of sarcoidosis in the presence of
asymptomatic
B.H.L.
Mount Sinai School of Medicine, New York, N.Y. 10029, U.S.A.
LOUIS E. SILTZBACH.
the patient’s history is insufficient evidence that he has received no anti-leprosy treatment. This is not to say that either our patients or Dr Rea’s were lying: some might have received treatment but not been informed of the diagnosis. Furthermore, a number of drugs other than sulphones (including sulphonamides, streptomycin, thiacetazone, and rifampicin) possess sufficient activity against Mycobacterium leprce to precipitate E.N.L. in patients with lepromatous leprosy. In the absence of objective data concerning the treatment status of the patients, there would not seem to be a sufficient basis for postulating that other factors such as cell-mediated immunity were important in the precipitation of E.N.L. M.R.C. Leprosy Project, Armauer Hansen Research Institute, and All-Africa Leprosy and Rehabilitation Training Centre, P.O. Box 1005, Addis Ababa, Ethiopia.
T. GODAL J. M. H. PEARSON W. F. Ross.
SPERM-COUNTS AFTER VASECTOMY
SiR,—The findings reported by Dr Cornes (March 31,
721) raise two questions. Was it possible to confirm parenthood after vasectomy ? Were the occasional sperms
p.
demonstrated in the stained films a common or an unusual at the appropriate interval after vasectomy ?
finding
Group Laboratory, St. Peter’s Hospital,
Chertsey, Surrey KT16 0PZ.
* ** We showed this letter follows.-ED. L.
ROBERT
to
J. EVANS.
Dr Cornes, whose
reply
SiR,—The point I
was trying to make was that spermafter vasectomy often fail to reveal the occasional sperm seen in the cytological examination of a stained smear. We find sperms present in at least one out of every 7-8 specimens received two months after vasectomy. We have a few patients with negative counts but positive smears one year after the operation. To anyone working in the infertility field, where spermcounts below 20 million per ml. are considered abnormal, the finding of a single sperm in a stained smear seems an impossible cause for pregnancy. However, medicolegally only 1 sperm is required, and the men concerned have already demonstrated their fertility. In the three cases of pregnancy following vasectomy which I referred to no parenthood test was carried out, but the clinicians concerned thought that extramarital causes were not implicated in any of them.
counts
Bristol General Hospital, Bristol BS1 6SY.
JOHN S. CORNES.
ERYTHEMA NODOSUM LEPROSUM IN THE ABSENCE OF CHEMOTHERAPY
SIR,-Dr Rea and his colleaguesreport 10 cases of erythema nodosum leprosum (E.N.L.) in lepromatous patients in the United States who claimed that they were not on sulphone treatment at the time the E.N.L. symptoms developed. However, in a recent study here, sulphone was detected in the urine of 8 out of 40 leprosy patients who claimed that they had not taken any anti-leprosy drug when attending this hospital for the first time. Thus, even in
a
developing
country with limited medical resources,
Hurley, T. H., Lane, W. R. Lancet, 1971, ii, 1373. Izumi, T., et al. VIth International Conference on Sarcoidosis, Tokyo, September, 1972 (in the press). 5. Chretian, J. Reports of European Symposium on Sarcoidosis; p. 9. Geneva, 1972. 6. Bringel, C. ibid. p. 34. 7. Rea, T. H., Levan, N. E., Schweitzer, R. E. Lancet, 1972, ii, 1252.
3. 4.
EVALUATION OF KIDNEY-PRESERVATION METHODS
SiR,—The report of Clark et al. indicating that immedifunction and one-year graft survival of cadaveric renal allografts were much better if the kidneys were preserved with Collins solution rather than by continuous perfusion (Belzer method) deserves comment. They reported one-year graft survival-rates for kidneys preserved by the Collins method and the Belzer method of 58% and 48%, respectively. Onset of function was immediate in 65% of the kidneys stored with Collins solution, compared with only 40% with the Belzer method. In view of the experimental evidence indicating that continuous hypothermic perfusion ate
is a more effective method of renal preservation, particularly of kidneys subjected to prepreservation warm ischaemia, these results are somewhat surprising. Since we feel that the clinical observations of Clark and his associates do not accurately reflect the effectiveness of renal preservation by continuous perfusion, we submit our clinical experience for
comparative
purposes.
transplants, from adult cadaveric years at the University of Cincinnati Medical Center, were studied. To be able to compare our results with those of Clark et al., kidney allografts were divided into the same 3 functional groups. The data are presented in the accompanying table. For the entire series, the mean preservation time was 14-7 hours (range 3-39 hours) and the mean warm ischasmia time was 21 minutes (range 5-60 minutes). Immediate function (group i) occurred in 32 (63%) of 51 kidneys with a mean Data
on
all 51 first renal
donors, performed
over
two
serum-creatinine of 1-5 mg. per 100 ml. at one month. If one compares this with Clark et al.’s results, for the same preservation interval, only 10 (31 %) of 32 kidneys functioned immediately. What is even more striking, we had only 1 kidney that failed to function at one month. This patient had an accelerated rejection and the graft was removed three weeks after transplant. By comparison, 8 (25%) of 32 of the kidneys in Clark et al.’s series failed by one month
post-transplant. In group II (those requiring dialysis during the first month), 9 patients had a mean serum-creatinine at one month greater than 3-0 mg. per 100 ml. Most, but not all, were a result of rejection phenomena. The other 9 patients, with no or slight rejection, had a mean serum-creatinine at one month of 1-6 mg. per 100 ml. Using continuous perfusion preservation, our overall one-year graft survival was 70 °o, compared with 48 °oreported by Clark et al. Since our experience has been very different from those 1.
E. A., Mickey, M. R., Opelz, G., Terasaki, P. I. Lancet, Feb. 17, 1973, p. 361.
Clark,
881 EVALUATION OF BELZER-PRESERVED CADAVER KIDNEYS AT ONE MONTH AFTER TRANSPLANT
* 1. Immediate function; no 2. Delayed function; some
’
dialysis required. dialysis required during
function at one month. 3. Failure of kidney at one month for any
We agree that preservation methods by simple cooling procedures, as advocated by Collins, are simpler and less expensive, and are effective in preserving undamaged kidneys for a short time. However, it must be emphasised that these methods are ineffective in the laboratory if one attempts 24-hour preservation of kidneys subjected to prepreservation warm ischaemia.7,8 Our experience with continuous perfusion is very different from that reported by Clark et al., indicating that their evaluation of Belzerpreserved kidneys may not have been ideal.
first
month, good
reason.
included in Clark et al.’s report, what are some possible factors accounting for the differences ? Besides the collection of data from several transplant centres, there are two important points that need emphasis. First, the authors state that using continuous perfusion one should be able to evaluate potential organ viability based on perfusion characteristics and, therefore, discard those kidneys that are likely not to function after transplantation. From failurerates of Belzer-preserved kidneys, they concluded that perfusion characteristics were not effective in evaluating potential function. However, they present no information defining the perfusion criteria by which the various centres evaluated potential renal function. We would argue that before perfusion characteristics are considered worthless, when used as an evaluative procedure, the criteria used to assess the functional capacity of a kidney need to be collated. With the shortage of cadaver kidneys, surgeons are likely to transplant a marginal kidney based on perfusion characteristics rather than discard the organ, thus negating one of the primary advantages of perfusion preservation. We have discarded 20 (15%) of 129 kidneys on the basis of abnormal perfusion characteristics, particularly high diastolic pressure (greater than 36-40 mm. Hg) and low flow-rates (less than 80 ml. per min. per kidney). Granted that these are gross estimations of potential function, one must adhere to these principles if the " viability testing " aspect of perfusion preservation is going to be effective in discerning the poor functioning kidney. To further define haemodynamic parameters of organ perfusion, we have studied the intrarenal distribution of perfusate flow in cadaver kidneys using radioactive microspheres. When kidneys with poor initial perfusion characteristics and with subsequent improvement (flow-rates > 100 ml. per min. per kidney) were studied, it was found that outer cortical flow was greatly decreased, even though total flow was normal. Experimentally, prepreservation warm ischaemia results in altered intrarenal flow patterns (decrease in outer cortical flow) which is associated with impaired renal function after transplantation. 2,3Therefore, initial flow-rates are probably the most important for assessment of potential renal function. The second important factor influencing the outcome of preserved cadaver kidneys, which was not available in Clark et al.’s papers, is the pretreatment of donors before nephrectomy. It is well known that release of catecholamines produces vasospasm which can severely alter renal function; and, therefore, a-adrenergic blocking agents such as phentolamine (’Rogitine ’)4 or phenoxybenzamine5 should be used. We have also shown that large doses (30 mg. per kg.) of methylprednisolone sodium succinate reduces ischaemic injury and improves initial renal function, if given two hours before the ischxmic insult.6
Department of Surgery and Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45229, U.S.A.
H. CHARLES MILLER J. WESLEY ALEXANDER E. J. SMITH.
centres
2. 3. 4. 5.
Miller, H. C., Alexander, J. W., Nathan, P. Surgery, 1972, 72, 193. Miller, H. C., Alexander, J. W. Transplant. Proc. 1972, 4, 595. Miller, H. C., Alexander, J. W. Surg. Forum, 1972, 23, 273. Belzer, F. O., Reed, T. W., Pryor, J. P., Kountz, S. L., Dunphy, J. L. Surg. Gynec. Obstet. 1970, 130, 467. 6. Miller, H. C., Alexander, J. W. Transplantation (in the press).
TALKING POLITICS
SIR,-We write to welcome your column by David McKie on Talking Politics, and in particular the informative article (April 7, p. 765) on the Commons Committee which is now working on the N.H.S. Reorganisation Bill. We should like to point out, however, that a curious but welcome Freudian slip seems to have crept into the report of Dr Vaughan’s fears about the current proposals. If only there were some proposals to the effect that district management teams might " descend, Big Brother-like, on the area authority " and not the other way round ! This opens up the exciting vision of community health councils also descending upon area health authorities, of area authorities descending upon the regional authorities, and the regions in turn descending upon the Department of Health, on Parliament-perhaps even on the Treasury itself Maybe the Commons Committee could pursue this idea and make the decision-takers at different levels in the new N.H.S. properly accountable to those affected by their decisions. More seriously, if the committee could consider exactly what is now meant by parliamentary accountability " for health matters, this would be most useful-it is highly relevant to the Bill with all its provisions for massive central control. We have just witnessed tax changes in respect of toothbrushes and sweets, cigars, and cigarettes which seem to indicate that the Treasury either knows little about health or, worse, that it knows but does not care. The Second Reading of the N.H.S. Reorganisation Bill in the Commons, particularly on the second day, was an impressive performance. But debate is one thing-accountability another. "
Department of
Community Medicine, Guy’s Hospital Medical School, London Bridge, SE1 9RT.
PETER DRAPER TONY SMART.
USE OF HOSPITAL RESOURCES
SIR,-Organisation of medical work in the hospitals of Liverpool is very bad; above all there are far too many hospital beds, especially in gynxcology. In the Women’s Hospital there are 18 consultant sessions for gynxcologists. In 1972 there were 103 available beds to which 3971 patients were admitted, giving a bed-occupancy of 79% with an average stay of seven days, or so I am informed. More than 3000 surgical specimens were sent to me for histological examination, and 6417 new outpatients were seen. My clinical colleagues are fully aware of the error of their ways : have you not told them of it ? B., Ackermann, J., Finch, W. T., Manlove, A. Lancet, 1970, i, 620. 8. Scott, D. F., Stephens, F. O., Keaveny, T. V., Kountz, S. L., Belzer, F. O. Transplantation, 1971, 2, 90. 7. Frost, A.
idiopathic pulmonary fibrosis, lung carcinoma, and collagen disorders.4-6 There is a strong likelihood, then, that Israel and Goldstein’s findings were equally nonspecific and had resulted from the use of an unsatisfactory sema,
bulk batch of Kveim material. In sum, I think that we have not yet arrived at a position where we can safely make a-priori diagnoses of sarcoidosis in the presence of
asymptomatic
B.H.L.
Mount Sinai School of Medicine, New York, N.Y. 10029, U.S.A.
LOUIS E. SILTZBACH.
the patient’s history is insufficient evidence that he has received no anti-leprosy treatment. This is not to say that either our patients or Dr Rea’s were lying: some might have received treatment but not been informed of the diagnosis. Furthermore, a number of drugs other than sulphones (including sulphonamides, streptomycin, thiacetazone, and rifampicin) possess sufficient activity against Mycobacterium leprce to precipitate E.N.L. in patients with lepromatous leprosy. In the absence of objective data concerning the treatment status of the patients, there would not seem to be a sufficient basis for postulating that other factors such as cell-mediated immunity were important in the precipitation of E.N.L. M.R.C. Leprosy Project, Armauer Hansen Research Institute, and All-Africa Leprosy and Rehabilitation Training Centre, P.O. Box 1005, Addis Ababa, Ethiopia.
T. GODAL J. M. H. PEARSON W. F. Ross.
SPERM-COUNTS AFTER VASECTOMY
SiR,—The findings reported by Dr Cornes (March 31,
721) raise two questions. Was it possible to confirm parenthood after vasectomy ? Were the occasional sperms
p.
demonstrated in the stained films a common or an unusual at the appropriate interval after vasectomy ?
finding
Group Laboratory, St. Peter’s Hospital,
Chertsey, Surrey KT16 0PZ.
* ** We showed this letter follows.-ED. L.
ROBERT
to
J. EVANS.
Dr Cornes, whose
reply
SiR,—The point I
was trying to make was that spermafter vasectomy often fail to reveal the occasional sperm seen in the cytological examination of a stained smear. We find sperms present in at least one out of every 7-8 specimens received two months after vasectomy. We have a few patients with negative counts but positive smears one year after the operation. To anyone working in the infertility field, where spermcounts below 20 million per ml. are considered abnormal, the finding of a single sperm in a stained smear seems an impossible cause for pregnancy. However, medicolegally only 1 sperm is required, and the men concerned have already demonstrated their fertility. In the three cases of pregnancy following vasectomy which I referred to no parenthood test was carried out, but the clinicians concerned thought that extramarital causes were not implicated in any of them.
counts
Bristol General Hospital, Bristol BS1 6SY.
JOHN S. CORNES.
ERYTHEMA NODOSUM LEPROSUM IN THE ABSENCE OF CHEMOTHERAPY
SIR,-Dr Rea and his colleaguesreport 10 cases of erythema nodosum leprosum (E.N.L.) in lepromatous patients in the United States who claimed that they were not on sulphone treatment at the time the E.N.L. symptoms developed. However, in a recent study here, sulphone was detected in the urine of 8 out of 40 leprosy patients who claimed that they had not taken any anti-leprosy drug when attending this hospital for the first time. Thus, even in
a
developing
country with limited medical resources,
Hurley, T. H., Lane, W. R. Lancet, 1971, ii, 1373. Izumi, T., et al. VIth International Conference on Sarcoidosis, Tokyo, September, 1972 (in the press). 5. Chretian, J. Reports of European Symposium on Sarcoidosis; p. 9. Geneva, 1972. 6. Bringel, C. ibid. p. 34. 7. Rea, T. H., Levan, N. E., Schweitzer, R. E. Lancet, 1972, ii, 1252.
3. 4.
EVALUATION OF KIDNEY-PRESERVATION METHODS
SiR,—The report of Clark et al. indicating that immedifunction and one-year graft survival of cadaveric renal allografts were much better if the kidneys were preserved with Collins solution rather than by continuous perfusion (Belzer method) deserves comment. They reported one-year graft survival-rates for kidneys preserved by the Collins method and the Belzer method of 58% and 48%, respectively. Onset of function was immediate in 65% of the kidneys stored with Collins solution, compared with only 40% with the Belzer method. In view of the experimental evidence indicating that continuous hypothermic perfusion ate
is a more effective method of renal preservation, particularly of kidneys subjected to prepreservation warm ischaemia, these results are somewhat surprising. Since we feel that the clinical observations of Clark and his associates do not accurately reflect the effectiveness of renal preservation by continuous perfusion, we submit our clinical experience for
comparative
purposes.
transplants, from adult cadaveric years at the University of Cincinnati Medical Center, were studied. To be able to compare our results with those of Clark et al., kidney allografts were divided into the same 3 functional groups. The data are presented in the accompanying table. For the entire series, the mean preservation time was 14-7 hours (range 3-39 hours) and the mean warm ischasmia time was 21 minutes (range 5-60 minutes). Immediate function (group i) occurred in 32 (63%) of 51 kidneys with a mean Data
on
all 51 first renal
donors, performed
over
two
serum-creatinine of 1-5 mg. per 100 ml. at one month. If one compares this with Clark et al.’s results, for the same preservation interval, only 10 (31 %) of 32 kidneys functioned immediately. What is even more striking, we had only 1 kidney that failed to function at one month. This patient had an accelerated rejection and the graft was removed three weeks after transplant. By comparison, 8 (25%) of 32 of the kidneys in Clark et al.’s series failed by one month
post-transplant. In group II (those requiring dialysis during the first month), 9 patients had a mean serum-creatinine at one month greater than 3-0 mg. per 100 ml. Most, but not all, were a result of rejection phenomena. The other 9 patients, with no or slight rejection, had a mean serum-creatinine at one month of 1-6 mg. per 100 ml. Using continuous perfusion preservation, our overall one-year graft survival was 70 °o, compared with 48 °oreported by Clark et al. Since our experience has been very different from those 1.
E. A., Mickey, M. R., Opelz, G., Terasaki, P. I. Lancet, Feb. 17, 1973, p. 361.
Clark,
881 EVALUATION OF BELZER-PRESERVED CADAVER KIDNEYS AT ONE MONTH AFTER TRANSPLANT
* 1. Immediate function; no 2. Delayed function; some
’
dialysis required. dialysis required during
function at one month. 3. Failure of kidney at one month for any
We agree that preservation methods by simple cooling procedures, as advocated by Collins, are simpler and less expensive, and are effective in preserving undamaged kidneys for a short time. However, it must be emphasised that these methods are ineffective in the laboratory if one attempts 24-hour preservation of kidneys subjected to prepreservation warm ischaemia.7,8 Our experience with continuous perfusion is very different from that reported by Clark et al., indicating that their evaluation of Belzerpreserved kidneys may not have been ideal.
first
month, good
reason.
included in Clark et al.’s report, what are some possible factors accounting for the differences ? Besides the collection of data from several transplant centres, there are two important points that need emphasis. First, the authors state that using continuous perfusion one should be able to evaluate potential organ viability based on perfusion characteristics and, therefore, discard those kidneys that are likely not to function after transplantation. From failurerates of Belzer-preserved kidneys, they concluded that perfusion characteristics were not effective in evaluating potential function. However, they present no information defining the perfusion criteria by which the various centres evaluated potential renal function. We would argue that before perfusion characteristics are considered worthless, when used as an evaluative procedure, the criteria used to assess the functional capacity of a kidney need to be collated. With the shortage of cadaver kidneys, surgeons are likely to transplant a marginal kidney based on perfusion characteristics rather than discard the organ, thus negating one of the primary advantages of perfusion preservation. We have discarded 20 (15%) of 129 kidneys on the basis of abnormal perfusion characteristics, particularly high diastolic pressure (greater than 36-40 mm. Hg) and low flow-rates (less than 80 ml. per min. per kidney). Granted that these are gross estimations of potential function, one must adhere to these principles if the " viability testing " aspect of perfusion preservation is going to be effective in discerning the poor functioning kidney. To further define haemodynamic parameters of organ perfusion, we have studied the intrarenal distribution of perfusate flow in cadaver kidneys using radioactive microspheres. When kidneys with poor initial perfusion characteristics and with subsequent improvement (flow-rates > 100 ml. per min. per kidney) were studied, it was found that outer cortical flow was greatly decreased, even though total flow was normal. Experimentally, prepreservation warm ischaemia results in altered intrarenal flow patterns (decrease in outer cortical flow) which is associated with impaired renal function after transplantation. 2,3Therefore, initial flow-rates are probably the most important for assessment of potential renal function. The second important factor influencing the outcome of preserved cadaver kidneys, which was not available in Clark et al.’s papers, is the pretreatment of donors before nephrectomy. It is well known that release of catecholamines produces vasospasm which can severely alter renal function; and, therefore, a-adrenergic blocking agents such as phentolamine (’Rogitine ’)4 or phenoxybenzamine5 should be used. We have also shown that large doses (30 mg. per kg.) of methylprednisolone sodium succinate reduces ischaemic injury and improves initial renal function, if given two hours before the ischxmic insult.6
Department of Surgery and Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45229, U.S.A.
H. CHARLES MILLER J. WESLEY ALEXANDER E. J. SMITH.
centres
2. 3. 4. 5.
Miller, H. C., Alexander, J. W., Nathan, P. Surgery, 1972, 72, 193. Miller, H. C., Alexander, J. W. Transplant. Proc. 1972, 4, 595. Miller, H. C., Alexander, J. W. Surg. Forum, 1972, 23, 273. Belzer, F. O., Reed, T. W., Pryor, J. P., Kountz, S. L., Dunphy, J. L. Surg. Gynec. Obstet. 1970, 130, 467. 6. Miller, H. C., Alexander, J. W. Transplantation (in the press).
TALKING POLITICS
SIR,-We write to welcome your column by David McKie on Talking Politics, and in particular the informative article (April 7, p. 765) on the Commons Committee which is now working on the N.H.S. Reorganisation Bill. We should like to point out, however, that a curious but welcome Freudian slip seems to have crept into the report of Dr Vaughan’s fears about the current proposals. If only there were some proposals to the effect that district management teams might " descend, Big Brother-like, on the area authority " and not the other way round ! This opens up the exciting vision of community health councils also descending upon area health authorities, of area authorities descending upon the regional authorities, and the regions in turn descending upon the Department of Health, on Parliament-perhaps even on the Treasury itself Maybe the Commons Committee could pursue this idea and make the decision-takers at different levels in the new N.H.S. properly accountable to those affected by their decisions. More seriously, if the committee could consider exactly what is now meant by parliamentary accountability " for health matters, this would be most useful-it is highly relevant to the Bill with all its provisions for massive central control. We have just witnessed tax changes in respect of toothbrushes and sweets, cigars, and cigarettes which seem to indicate that the Treasury either knows little about health or, worse, that it knows but does not care. The Second Reading of the N.H.S. Reorganisation Bill in the Commons, particularly on the second day, was an impressive performance. But debate is one thing-accountability another. "
Department of
Community Medicine, Guy’s Hospital Medical School, London Bridge, SE1 9RT.
PETER DRAPER TONY SMART.
USE OF HOSPITAL RESOURCES
SIR,-Organisation of medical work in the hospitals of Liverpool is very bad; above all there are far too many hospital beds, especially in gynxcology. In the Women’s Hospital there are 18 consultant sessions for gynxcologists. In 1972 there were 103 available beds to which 3971 patients were admitted, giving a bed-occupancy of 79% with an average stay of seven days, or so I am informed. More than 3000 surgical specimens were sent to me for histological examination, and 6417 new outpatients were seen. My clinical colleagues are fully aware of the error of their ways : have you not told them of it ? B., Ackermann, J., Finch, W. T., Manlove, A. Lancet, 1970, i, 620. 8. Scott, D. F., Stephens, F. O., Keaveny, T. V., Kountz, S. L., Belzer, F. O. Transplantation, 1971, 2, 90. 7. Frost, A.